The proposed research will evaluate the role of gamma-carboxyglutamic acid in the binding of calcium ion and phospholipid to prothrombin and Factor IX. Studies will initially utilize synthetic polypeptides and natural peptides, obtained by degradation of prothrombin, as models for the study of the native proteins. The role of gamma-carboxyglutamyl residues will be evaluated by chemical modification and by physical measurements on fragments of increasing size including the native proteins. The structure-function data derived from these studies will be applied to the investigation of a series of Factor IX mutants derived from patients with known blood coagulation disorders.